This project is designed to investigate the mechanisms controlling the rate of growth of neutrophilic granulocytes under physiological and pathologic conditions. The studies outlined in this request are designed to delineate mechanisms controlling the following aspects of neutrophil kinetics; 1) control of the rate of release of mature neutrophils from bone marrow to blood, 2) control of the size and mitotic rate in the myelocyte-promyelocyte-myeloblast compartment of the bone marrow and, 3) control of the size, mitotic rate and of outflow from the pluripotential stem cell compartment. Concurrently, with the determination of physiological control mechanisms for the normal system, we will attempt to determine specific defects in neutrophil control which may be associated with various diseases in man.